Search Results (6)

Canine hepatocellular carcinoma (HCC) is characterized by distinct computed tomography (CT) findings. HCC exhibits tumor heterogeneity, with different genomic information and histopathological features within the same tumor. In human HCC, genetic alterations affect the prognosis and treatment, and research has begun to assess genetic alterations using minimally invasive and reproducible CT. However, the relationship between CT findings and the genomic information of canine HCC is unknown. Early contrast of HCC indicates increased intratumoral neovascular growth. In this study, we aimed to investigate the relationship between enhancement patterns in the arterial phase of CT imaging and gene expression in canine HCC using RNA sequencing. Based on the CT findings, three of the eight dogs studied were classified as having enhancement HCC and five as having non-enhancement HCC. RNA sequencing was performed using the mRNA extracted from the specimens. Eight differentially expressed genes met the cutoff criteria. Among these, DUSP9, SLPI, and ALDH1L2 were the most upregulated genes in enhancement HCC, whereas SLC1A1 was the most downregulated in non-enhancement HCC. Canine HCC may involve different angiogenesis mechanisms. CT findings can be used to assess the gene expression status in canine HCC and may add new value to CT imaging. Full article

Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) can be difficult to differentiate but must be diagnosed correctly as treatment and prognosis for these tumors differ markedly. Relevant diagnostic biomarkers are thus needed, and those identified in dogs may have utility in human medicine because of the similarities between human and canine HCA and HCC. A tRNA-derived fragment (tRF), tRNA-Val, is a promising potential biomarker for canine mammary gland tumors but has not previously been investigated in hepatic tumors. Accordingly, we aimed to elucidate the potential utility of tRNA-Val as a biomarker for canine HCA and HCC using clinical samples (tumor tissue and plasma extracellular vesicles [EVs]) and tumor cell lines with qRT-PCR assays. We also investigated relevant functions and signaling pathways with bioinformatic analyses (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes). tRNA-Val was markedly downregulated in HCC tumor tissue versus HCA tumor tissue and normal liver tissue, and a similar trend was shown in plasma EVs and HCC cell lines versus healthy controls. Based on areas under the receiver operating characteristic curves (AUCs), tRNA-Val significantly distinguished HCC (AUC = 1.00, p = 0.001) from healthy controls in plasma EVs and HCC from HCA (AUC = 0.950, p = 0.01). Bioinformatics analysis revealed that tRNA-Val may be primarily involved in DNA repair, mRNA processing, and splicing and may be linked to the N-glycan and ubiquitin-mediated proteasome pathways. This is the first report on the expression of tRNA-Val in canine HCC and HCA and its possible functions and signaling pathways. We suggest that tRNA-Val could be a promising novel biomarker to distinguish canine HCC from HCA. This study provides evidence for a greater understanding of the role played by tRNA-Val in the development of canine HCC. Full article

Hepatocellular carcinomas (HCC) are common tumors, whereas hepatocellular adenomas (HCA) are rare, benign tumors in dogs. The aberrant expression of noncoding RNAs (ncRNAs) plays a pivotal role in HCC tumorigenesis and progression. Among ncRNAs, micro RNAs have been widely researched in human HCC, but much less widely in canine HCC. However, Y RNA-derived fragments have yet to be investigated in canine HCC and HCA. This study targeted canine HCC and HCA patients. We used qRT-PCR to determine Y RNA expression in clinical tissues, plasma, and plasma extracellular vesicles, and two HCC cell lines (95-1044 and AZACH). Y RNA was significantly decreased in tissue, plasma, and plasma extracellular vesicles for canine HCC versus canine HCA and healthy controls. Y RNA was decreased in 95-1044 and AZACH cells versus normal liver tissue and in AZACH versus 95-1044 cells. In plasma samples, Y RNA levels were decreased in HCC versus HCA and Healthy controls and increased in HCA versus Healthy controls. Receiver operating characteristic analysis showed that Y RNA could be a promising biomarker for distinguishing HCC from HCA and healthy controls. Overall, the dysregulated expression of Y RNA can distinguish canine HCC from HCA. However, further research is necessary to elucidate the underlying Y RNA-related molecular mechanisms in hepatocellular neoplastic diseases. To the best of our knowledge, this is the first report on the relative expression of Y RNA in canine HCC and HCA. Full article

Background: Hepatocellular carcinoma (HCC) in dogs is uncommon and often associated with a good prognosis, although some cases prove to be aggressive. In human oncology HCC is often very aggressive and diagnostic methods and prognostic factors are widely used to predict its biological behaviour. These include the expression of PIVKA-II. Methods: in order to identify a prognostic factor for canine HCC, we applied different methods of histological grading and investigated PIVKA-II expression in 22 HCC of dogs treated surgically and followed clinically for at least 2 years. Results: Nineteen patients analysed have passed the observation period without tumour recurrence, while 3 died following the development of metastases. PIVKA-II was positive in 15/22 cases without correlation with prognosis or tumoural grading even if a trend of PIVKA-II negativity in low WHO grades as well as increased number of PIVKA-II positive cases in higher WHO grades weres observed. Conclusions: This work showed that, PIVKA-II cannot be considered either as a marker of malignancy or as a prognostic marker for canine HCC. The poor prognosis depends usually on the clinical presentation. Thus prognostic parameters in canine HCC able to predict its aggressive behaviour through histological examination are still missing. The most promising method, limited to our study, seems to be the WHO histological grading. Full article

Chronic hepatitis and hepatocellular carcinoma (HCC) caused by the hepadnavirus hepatitis B virus (HBV) are significant causes of human mortality. A hepatitis-B-like virus infecting cats, domestic cat hepadnavirus (DCH), was reported in 2018. DCH DNA is hepatotropic and detectable in feline blood or serum (3.2 to 12.3%). Detection of HBV DNA has been reported in sera from 10% of free-roaming dogs in Brazil, whereas 6.3% of sera from dogs in Italy tested positive for DCH DNA by real-time quantitative PCR (qPCR). If DCH, HBV, or another hepadnavirus is hepatotropic in dogs, a role for such a virus in the etiology of canine idiopathic chronic hepatitis (CH) or HCC warrants investigation. This study investigated whether DCH DNA could be detected via qPCR in blood from dogs in Hong Kong and also whether liver biopsies from dogs with confirmed idiopathic CH or HCC contained hepadnaviral DNA using two panhepadnavirus conventional PCRs (cPCR) and a DCH-specific cPCR. DCH DNA was amplified from 2 of 501 (0.4%) canine whole-blood DNA samples. A second sample taken 6 or 7 months later from each dog tested negative in DCH qPCR. DNA extracted from 101 liver biopsies from dogs in Hong Kong or the USA, diagnosed by board-certified pathologists as idiopathic CH (n = 47) or HCC (n = 54), tested negative for DCH DNA and also tested negative using panhepadnavirus cPCRs. This study confirms that DCH DNA can be detected in canine blood by qPCR, although at a much lower prevalence than that reported previously. We identified no evidence to support a pathogenic role for a hepadnavirus in canine idiopathic CH or HCC. Full article

The Density Functional Theory (DFT) method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS) and principal component regression (PCR) models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R² = ±0.0106, R²_ajust = ±0.0125, s = ±0.0234, F_(4,11) = ±12.7802, Q² = ±0.0088, SEV = ±0.0132, PRESS = ±0.4808 and S_PRESS = ±0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set) with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA), cellular permeability (P_CaCO2), cell permeability Maden Darby Canine Kidney (P_MDCK), skin permeability (P_Skin), plasma protein binding (PPB) and penetration of the blood-brain barrier (C_Brain/Blood), and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers. Full article